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Primary biliary cholangitis (PBC) is a cholestatic autoimmune liver disease characterized by autoreactive T cell response against intrahepatic small bile ducts. Here, we use Il12b-/-Il2ra-/- mice (DKO mice) as a model of autoimmune cholangitis and demonstrate that Cd8a knockout or treatment with an anti-CD8α antibody prevents/reduces biliary immunopathology. Using single-cell RNA sequencing analysis, we identified CD8+ tissue-resident memory T (Trm) cells in the livers of DKO mice, which highly express activation- and cytotoxicity-associated markers and induce apoptosis of bile duct epithelial cells. Liver CD8+ Trm cells also upregulate the expression of several immune checkpoint molecules, including PD-1. We describe the development of a chimeric antigen receptor to target PD-1-expressing CD8+ Trm cells. Treatment of DKO mice with PD-1-targeting CAR-T cells selectively depleted liver CD8+ Trm cells and alleviated autoimmune cholangitis. Our work highlights the pathogenic role of CD8+ Trm cells and the potential therapeutic usage of PD-1-targeting CAR-T cells.

Abstract Objective We sought to explore the linear or nonlinear relationship between preoperative iron metabolism and acute kidney injury following cardiac surgery (CSA-AKI) with cardiopulmonary bypass (CPB). Methods Patients who underwent cardiac surgery with CPB between December 2018 and April 2021 were retrospectively collected from Fuwai Hospital and Medical Information Mart for Intensive Cared dataset (MIMIC-IV). The measurements of iron metabolism included serum iron (SI), serum ferritin (SF), transferrin (TRF), transferrin saturation (TS), and total iron binding capacity (TIBC). Logistic regression and restricted cubic spline (RCS) were used for linear and nonlinear analysis. The primary outcome was postoperative AKI with 48 h after cardiac surgery. Results Of 10,639 patients screened (2420 in Fuwai Hospital and 8219 in MIMIC-IV dataset),1488 eligible patients were enrolled for the final analysis (Fuwai Hospital: n = 744, MIMIC-IV: n = 744).The incidence of AKI was 25.7% and 56.5%, respectively. Logistic regression showed that the levels of TRF (odds ratio (OR) = 1.53,95%CI:1.01–2.14, p = 0.012) and TIBC (OR = 1.05,95%CI:1.02–1.07, p

Abstract Background Interleukin-10 (IL-10), a pivotal anti-inflammatory cytokine, has gotten attention for its involvement in tissue remodeling and organ fibrosis. Pleurisy and subsequent pleural remodeling are recognized as quantifiable indicators of systemic lupus erythematosus (SLE) activity. However, the role of IL-10 in SLE-associated pleural remodeling remains unknown. In this study, we investigated role of IL-10 in SLE-associated pleural remodeling and the underlying mechanism. Methods Clinical data and serum specimens were obtained from SLE patients, while pleural mesothelial cells and mouse models served as primary experimental subjects. The protein expression-related technologies, histopathological staining, and other experimental methods were used in the study. Results Our investigation got several key findings. Firstly, serum obtained from SLE patients with pleural thickening was found to induce pleural mesothelial cell remodeling. Subsequently, heightened levels of IL-10 were found in serum from SLE patients with pleural thickening compared to that of SLE patients without pleural thickening. Secondly, administration of recombinant IL-10 was confirmed its ability to induce pleural mesothelial cell remodeling, on the contrary, this remodeling was effectively mitigated by IL-10 inhibition. Notably, blockade of IL-10 significantly prevented collagen deposition and prevented thickening in pleura of SLE mouse models. Lastly, the IL-10/JAK2/STAT3/HIF1α/TMEM45A/P4HA1 signaling axis was elucidated to mediate pleural remodeling and thickening. Conclusions Our study uncovered that IL-10 mediated pleural remodeling in SLE. We suggested that serum IL-10 level exceeding 6.32 pg/mL was a potential reference threshold for predicting pleural thickening in SLE patients.

Chromium (III) is an essential trace element for the human body. It modulates the synthesis, secretion, and content of insulin in the body. In addition to participating in the regulation of glucose and lipid metabolism, it performs various important physiological functions, including the reduction of glucose and lipid levels. Glucose and lipid metabolism disorders are the cause of many chronic diseases and have a complex pathogenesis. Research shows that chromium (III) is related to glucose and lipid metabolism. Therefore, this study performes a meta-analysis of studies related to the safety of chromium (III) and its influence on glucose and lipid metabolism and elucidated the mechanisms. Chromium (III) can enhance insulin sensitivity, promote glucose absorption and glycogen synthesis and improve insulin resistance by regulating AMPK/GLUT-4 and PI3K/Akt signaling pathways. And it also can improve lipid metabolism by regulating the expression of SREBP-1C, ACC1 and CD36. The article would provide a theoretical basis for the use of chromium (III) toward the prevention and treatment of metabolic diseases, such as diabetes mellitus and obesity, so that it could be further applied in the food industry.

Abstract The heat shock transcription factor (HSF) family is one of the most widely studied transcription factor families in plants; HSFs can participate in the response to various stressors, such as heat stress, high salt, and drought stress. Based on garlic transcriptome data, we screened and identified 22 garlic HSFs. The HSF proteins of garlic and Arabidopsis can be divided into three (A, B, C) subfamilies. The phylogenetic relationship, chromosome localization, sequence characteristics, conserved motifs, and promoter analysis of the HSF family were analyzed through bioinformatics methods. RT-qPCR analysis showed that the nine selected genes had different degrees of response to heat stress. In addition, we isolated and identified a class B HSF gene, AsHSFB1, from garlic variety ‘Xusuan No.6’. Subsequently, the AsHSFB1 gene was overexpressed in Arabidopsis thaliana. Under heat stress, the germination rate and growth of wild-type plants were better than that of transgenic plants. Moreover, after heat treatment, the contents of peroxidase, catalase, and chlorophyll a and b of transgenic plants were lower, but the contents of malondialdehyde (MDA) and leaf conductivity were higher. Nitroblue tetrazolium (NBT) staining showed that the stained area of transgenic plant leaves was larger than that of the wild type. Further studies showed that AsHSFB1 overexpression inhibited the expression of related reverse resistance genes. These results indicate that AsHSFB1 might play a negative regulatory role in garlic resistance under high stress. Altogether, these findings provide valuable data for revealing the function of HSF genes and lay a foundation for the subsequent selection of heat-resistant garlic varieties.

Abstract Lung adenocarcinoma (LUAD) is the major subtype of lung cancer. The poor prognosis of LUAD patients is attributed primarily to metastasis. ADAMTS16 is a crucial member of the ADAMTS family and is involved in tumor progression. However, its role and regulatory mechanism in LUAD remain unexplored. In this study, ADAMTS16 was identified as a crucial oncogene and survival predictor in LUAD via analyses of public datasets. Clinical specimens and tissue microarrays confirmed the differential expression and prognostic value of ADAMTS16 in LUAD patients. Transcriptome data and in vitro experiments demonstrated that ADAMTS16 was positively associated with epithelial-mesenchymal transition (EMT) and the migration abilities of LUAD cells. Knockdown of ADAMTS16 attenuated lung and pleural metastasis in an animal model. Mechanistically, the results of the enzyme-linked immunosorbent assay (ELISA) and western blot (WB) suggested that ADAMTS16 activated the TGF-β signaling pathway by facilitating the conversion of LAP-TGF-β1 to active TGF-β1. Co-Immunoprecipitation (co-IP) indicated an interaction between ADAMTS16 and LAP-TGF-β1. Inhibition of ADAMTS16 impaired EMT and aggressiveness of LUAD cells, while treatment with recombinant TGF-β1 reversed this inhibition. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays indicated that SOX4 acted as a transcriptional activator of ADAMTS16 and that TGF-β1 regulated the expression of ADAMTS16 by increasing the binding of SOX4 to the promoter of ADAMTS16. Suppressing the TGF-β signaling pathway inhibited ADAMTS16 expression, EMT, and lung metastasis, whereas overexpressing SOX4 reversed this inhibition. Therefore, ADAMTS16 forms a positive feedback loop with the TGF-β1/SOX4 axis to regulate EMT and metastasis, and disruption of this feedback loop inhibits tumor progression. These findings underscore the potential of ADAMTS16 as a prognostic biomarker and therapeutic target in LUAD and offer novel insight into the mechanism of EMT and metastasis.

Abstract Background Many studies have indicated that abnormal bone mineral density (BMD) is related to abnormal liver and kidney function, but the effect of serum albumin level on abnormal BMD and osteoporotic fracture is still controversial. The aim of this retrospective study was to investigate the effects of serum albumin levels on abnormal BMD and osteoporotic fractures. Methods The study included 538 patients through the electronic medical records of inpatients and outpatients stored at Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology. A multivariate logistic regression model was employed to test the relationship between serum albumin levels and abnormal BMD, and the effect of serum albumin levels on osteoporotic fractures was verified through the U test. Correlation between age, sex, kidney stones, coronary heart disease, hypertension, diabetes, fatty liver disease, haemoglobin (HB), mean corpuscular haemoglobin concentration (MCHC), platelets (PLT), platelet distribution width (PDW), lymphocytes (LYMP), alanine aminotransferase (ALT), total protein (TP), albumin (ALB), uric acid (UA), total bilirubin (TBIL), total cholesterol (TC), high-density lipoprotein (HDL) and abnormal BMD were analysed by logistic regression modelling after excluding confounding factors. Results The ALB level in osteoporotic patients was 41.70 (36.40–45.00) g/L, which was significantly lower than those in the normal BMD and reduced BMD groups. The odds ratio (OR) (95% confidence interval [CI]) between the osteoporosis and normal BMD groups was 0.445 (0.394–0.502); the OR (95% CI) between the osteoporosis and reduced BMD groups was 0.395 (0.341–0.459). In the subgroup analysis by whether or not a fracture was present, the OR (95% CI) was 0.073 (0.045–0.119). Conclusions ALB is a protective factor against osteoporosis and osteoporotic fractures, suggesting that it may have the potential to predict osteoporosis onset and fractures.

Abstract The impact of climate change on medicinal plants has significantly altered their suitable environments, thereby affecting the quality of herbal medicines. Notopterygium franchetii (N. franchetii), a medicinal plant intricately linked to its natural habitat, exhibits substantial quality variations influenced by the ecological conditions of its native region. In this study, comprehensive field surveys were conducted to gather occurrence records and samples of N. franchetii. The Maxent model and ArcGIS software were employed to predict the suitable habitats of N. franchetii during different time periods. A high-performance liquid chromatography (HPLC) method was developed to establish the chemical fingerprints of 21 sample batches. Fourteen common peaks were subjected to cluster analysis, principal component analysis, and orthogonal partial least squares-discriminant analysis. The findings revealed quality variations correlated with their geographic origins, identifying peaks 10, 1, 14, 3, and 4 as crucial for quality differentiation. The study indicates that precipitation, temperature, and altitude significantly influence the distribution of N. franchetii. Under current climate conditions, the suitable habitat area for N. franchetii is estimated to be approximately 94,637.33 km2. However, projections under three future climate scenarios suggest a declining trend in suitable habitat areas. A quality zoning map of N. franchetii was developed, integrating a correlation model between chemical composition and environmental variables with the spatial analysis and visualization capabilities of ArcGIS. The high-quality regions for N. franchetii are predominantly located in the Gannan, Linxia, Dingxi, Longnan, and Wuwei districts. These research outcomes offer a valuable reference for identifying suitable cultivation areas and assessing the quality of N. franchetii in Gansu Province.

Abstract Excessive intake of red meat may cause damage to colorectal tissue but not cause significant damage to the small intestine. However, the underlying mechanism is not clear. In this study, the effect of myoglobin extracted from red meat was explored on the intestinal barrier function of the mice, and its potential mechanism was elucidated through cell culture experiments. Exclusively high‐dose myoglobin (3.39%, equivalent to 450 g red meat per day for human) resulted in marked intestinal permeability with increased levels of serum endotoxin, diamine oxidase, and d‐lactate but reduced the mRNA levels of tight junction proteins and mucin 2 in the duodenal and colonic tissues. The diet also increased free iron and heme levels in the duodenal and colonic tissues, leading to higher level of oxidative stress and inflammatory response. Metabolomic analysis of colonic contents showed that exclusively high‐dose myoglobin altered the relative content of indole and its derivatives, phenolic compounds, and 5‐hydroxy‐l‐tryptophan by regulating tryptophan metabolism and kynurenine cycle and destroying intestinal homeostasis. The very high myoglobin hydrolysate induced oxidative stress and apoptosis more seriously in HT29 cells than in INT407 cells, which could be the main reason for more severe colon injury. Nevertheless, normal low‐dose intake (0.38% myoglobin, equivalent to 50 g per day for human) did not show the above‐mentioned harmful effects. The findings provided a risk assessment for the dosage of red meat intake and new insights into the relationship between red meat intake and intestinal health.

Abstract Background Diet may influence susceptibility of human papillomavirus (HPV) infection by affecting inflammation and immunity. However, the association between HPV infection and the inflammatory potential of diet has not been investigated. The research aimed to examine the correlation between HPV status and the dietary inflammatory index (DII®). Methods We utilized data from the National Health and Nutrition Examination Survey (NHANES) 2003–2016 to investigate the correlation between DII and HPV status among 9,256 women aged 18–59 years. DII scores were calculated based on 24-hour dietary recall interviews. The association between HPV status and DII was analyzed using weighted logistic regression and restricted cubic spline (RCS). Results Women with HPV infection exhibited higher DII scores than those without HPV infection. An increased likelihood of HPV infection was found to be significantly associated with higher DII scores (OR = 1.05, 95% CI: 1.01–1.09, P = 0.021), after full multivariate adjustment. Compared with the lowest tertile of DII scores, the ORs (95% CIs) for HPV infection were 1.20 (1.01, 1.42) and 1.27 (1.07, 1.51) for the second and third tertiles, respectively (P for trend = 0.006). RCS analysis showed a U-shaped relationship between DII and HPV infection, with a breakpoint identified at 0.13. Conclusions Our findings suggest that a pro-inflammatory diet is associated with an increased likelihood of HPV infection among women in the United States. Dietary interventions to reduce inflammation may help prevent HPV infection and related diseases.

With the increasing demand for large-scale, lightweight, and highly safe ocean transportation vessels and drilling equipment, as well as the growing need for environmentally friendly steels, the demand for high-strength, high-toughness, and weldable thick steel plates for ships and ocean engineering is becoming increasingly significant. However, as the strength and thickness of steel plates increase, the low-temperature toughness of the center of high-strength and extra-thick steel plates has become a significant challenge. Owing to low rolling reduction and central segregation in ultra-heavy plate steel, the poor low-temperature toughness of the central region poses a major challenge that limits the application of high-strength ultra-heavy steels. This work systematically investigated the effects of a two-step intercritical heat treatment on regulating the multiphase microstructure and properties of 100 mm EH500 marine engineering steel with severe central segregation. The results showed that after intercritical annealing in the 740 ℃ two-phase region, the experimental steel exhibited a yield strength of 540 MPa and a tensile strength of 869 MPa. However, the elongation and low-temperature toughness at −40 ℃ were relatively low, at only 5.1% and 14 J, respectively. Subsequent tempering at 600 ℃, 660 ℃, and 680 ℃ did not significantly alter the yield strength of the experimental steel, which remained within the range of 528 MPa to 551 MPa, while the tensile strength decreased to between 687 MPa and 730 MPa. The elongation and low-temperature toughness of the experimental steel initially increased and then decreased with the tempering temperature. At a tempering temperature of 660 ℃, the plasticity and toughness were optimized, with an elongation of 30.6% and a Charpy impact energy of 163 J at −40 ℃. Microstructure characterization results indicated that the experimental steel annealed at 740 ℃ consisted of intercritical ferrite (IF) and martensite (M). After further tempering at 600 ℃, a multi-phase microstructure comprising IF and tempered martensite (TM) with fine carbides was obtained. At a tempering temperature of 660℃, the microstructure of the experimental steel consisted of IF, TM, and fine retained austenite (RA). The RA content in the central segregation region was significantly higher than that in the matrix, resulting in a significant improvement in the plastic toughness of the experimental steel. With the further increase in the tempering temperature to 680 ℃, the experimental steel realized an IF and TM structure, with a small proportion of RA and a significant fraction of martensite/austenite (M/A) constituents in the central segregation zone. The large fraction of M/A constituents could substantially deteriorate the plasticity and toughness of the experimental steel.

Abstract Introduction For some patients with atopic dermatitis (AD), topical corticosteroids (TCS), topical calcineurin inhibitors (TCI), and systemic therapies are inadequate to control disease or are associated with adverse events (AEs). Ruxolitinib cream monotherapy demonstrated anti-inflammatory and anti-pruritic effects among patients enrolled in two pivotal phase 3 studies (TRuE-AD1/TRuE-AD2); most patients had long-term disease control with as-needed use during the 44-week long-term safety (LTS) period. This post hoc analysis explored efficacy and safety of 1.5% ruxolitinib cream by previous medication use. Methods Patients aged ≥ 12 years enrolled in TRuE-AD1/TRuE-AD2 were randomized 2:2:1 to twice-daily 0.75% or 1.5% ruxolitinib cream or vehicle cream for 8 weeks, followed by a 44-week LTS period; patients initially on vehicle were re-randomized 1:1 to either ruxolitinib cream strength. Results Within 12 months of enrollment (N = 1249), previous AD therapies were used by 89.4% of efficacy-evaluable patients applying vehicle or ruxolitinib cream (n = 725); of these, 80.4% received TCS (n = 583), 22.2% TCI (n = 161), 20.3% TCS + TCI (n = 147), and 18.9% systemic therapies (n = 137). Across previous medication subgroups, achievement of Investigator’s Global Assessment (IGA)-treatment success (IGA 0/1 with ≥ 2-grade improvement from baseline), ≥ 75% improvement in Eczema Area and Severity Index from baseline, and ≥ 4-point improvement in Itch numerical rating scale score from baseline at Week 8 did not substantially differ among patients who applied ruxolitinib cream. Outcomes were similar to those in the overall study population. At all study visits during the LTS period, > 70% of patients in each subgroup had IGA 0/1 and a low percentage (generally

Aiming at the problem that the traditional modeling methods cannot describe the real characteristics of flyback converters more accurately, the average state model of the fractional-order flyback converter operating in the intermittent inductance current mode was established by using fractional-order calculus and state space average method. The DC equilibrium point and small signal transfer function were obtained, and the difference between the model and the integer order mathematical model was compared. The state space model and circuit simulation model of fractional-order flyback converter were built in Simulink, and the experimental circuit of fractional-order flyback converter was constructed. The state space model, circuit model simulation and experimental results were compared to prove the correctness of the fractional-order model. The results show that the fractional order mathematical model can reflect the change of the order of inductance and capacitance, and the theoretical analysis is better consistent with the actual operation of the converter. A more accurate mathematical model of flyback converter can be established by combining fractional calculus theory with state space average method, which provides a reference for the modeling of other converters.

Abstract Background Previous studies have suggested an association between low serum bilirubin concentrations and increased risk of cognitive impairment. This study aimed to explore the association and dose-response relationship between serum direct bilirubin (DBIL) concentrations and mild cognitive impairment (MCI) among hemodialysis patients. Methods This is a multicenter cross-sectional study with patients undergoing hemodialysis from 22 dialysis centers in Guizhou Province, China. The outcome was mild cognitive impairment (MCI), measured with a Mini-Mental State Examination. The association and dose-response relationship between serum DBIL and MCI incidence were examined using multivariate logistic regression analysis, restricted cubic spline, and subgroup analysis to explore the association of serum DBIL concentrations with MCI. Results Of the 4223 enrolled patients (mean age 55.2 ± 15.3 years, 60.4% males), 1187 (28.1%) had MCI. Serum DBIL of 0.10-1.67umol/L [multivariable-adjusted odds ratios (OR) 1.32, 95% confidence interval (CI): 1.08–1.60, P = 0.005], 2.31-3.20umol/L (OR = 1.22, 95%CI: 1.00-1.49, P = 0.047), and > 3.21umol/L (OR = 1.32, 95%CI: 1.08–1.61, P = 0.006) had increased risk of MCI compared with 1.68-2.30umol/L. The dose-response analysis between serum DBIL and MCI showed a U-shaped relationship (P for non-linearity = 0.009), and the serum DBIL concentrations with the lowest risk of MCI was 2.01umol/L. As the serum DBIL concentrations were lower than the reference, the risk of MCI decreased by 49% per standard deviation (SD) increase in serum DBIL (OR = 0.51, 95%CI: 0.29–0.89, P

In this article, we aim to investigate the decay characteristics of a system consisting of two viscoelastic wave equations with Dirichlet boundary conditions, where the dispersion term and nonlinear weak damping term are taken into account. Under appropriate conditions, we establish both general and optimal decay results. This work generalizes and improves earlier results in the literature.

Abstract Avian feather intricate adaptable architecture to wing deformations has catalyzed interest in feathered flapping-wing aircraft with high maneuverability, agility, and stealth. Yet, to mimic avian integrated somatic sensation within stringent weight constraints, remains challenging. Here, we propose an avian-inspired embodied perception approach for biohybrid flapping-wing robots. Our feather-piezoelectric mechanoreceptor leverages feather-based vibration structures and flexible piezoelectric materials to refine and augment mechanoreception via coupled oscillator interactions and robust microstructure adhesion. Utilizing convolutional neural networks with the grey wolf optimizer, we develop tactile perception of airflow velocity and wing flapping frequency proprioception. This method also senses pitch angle via airflow direction and detects wing morphology through feather collisions. Our low-weight, accurate perception of flapping-wing robot flight states is validated by motion capture. This investigation constructs a biomechanically integrated embodied perception system in flapping-wing robots, which holds significant promise in reflex-based control of complex flight maneuvers and natural bird flight surveillance.

Abstract Background Gestational diabetes mellitus (GDM) is a common complication of mid–to-late pregnancy. Here, we constructed a predictive model for GDM based on a combination of clinical characteristics and relevant serum markers. Methods Data from full-term singleton vaginal deliveries from January 2022 to January 2023 were retrospectively collected from the obstetrics department. The data collected were segregated and assigned to training, validation, and external test sets. Maternal demographic characteristics, living and working habits, and haematological indicators, such as liver function and lipids were collected using a questionnaire designed for the study. The “rms” package in R was used to explore GDM-associated factors through stepwise regression at P 0.05. The ROC curve AUCs for the three groups were 0.93 (95% CI: 0.89–0.97), 0.72 (95% CI: 0.62–0.81), and 0.68 (95% CI: 0.53–0.83), respectively. Conclusion In this study, a GDM prediction model was constructed to achieve high performance in GDM risk prediction based on routine obstetric tests and information.

Abstract Background Geranyllinalool, a natural diterpenoid found in plants, has a floral and woody aroma, making it valuable in flavors and fragrances. Currently, its synthesis primarily depends on chemical methods, which are environmentally harmful and economically unsustainable. Microbial synthesis through metabolic engineering has shown potential for producing geranyllinalool. However, achieving efficient synthesis remains challenging owing to the limited availability of terpenoid precursors in microorganisms. Thus, an artificial isopentenol utilization pathway (IUP) was constructed and introduced in Escherichia coli to enhance precursor availability and further improve terpenoid synthesis. Results We first constructed an artificial IUP in E. coli to enhance the supply of precursor geranylgeranyl diphosphate (GGPP) and then screened geranyllinalool synthases from plants to achieve efficient synthesis of geranyllinalool (274.78 ± 2.48 mg/L). To further improve geranyllinalool synthesis, we optimized various cultivation factors, including carbon source, IPTG concentration, and prenol addition and obtained 447.51 ± 6.92 mg/L of geranyllinalool after 72 h of shaken flask fermentation. Moreover, a scaled-up production in a 5-L fermenter was investigated to give 2.06 g/L of geranyllinalool through fed-batch fermentation. To the best of our knowledge, this is the highest reported titer so far. Conclusions Efficient synthesis of geranyllinalool in E. coli can be achieved through a two-step pathway and optimization of culture conditions. The findings of this study provide valuable insights into the production of other terpenoids in E. coli.

Due to continuous application as a flavoring agent in the pesticide, pharmaceutical, and food industries, methyl eugenol (ME) persists in the environment and causes deleterious impacts including cytotoxicity, genotoxicity, and liver damage. This study utilized a comprehensive approach, integrating toxicokinetics, metabolomics, and gut microbiota analysis, to explore the mechanisms behind ME-induced hepatotoxicity in mice. The study observed significant rises in ALT and AST levels, along with significant weight loss, indicating severe liver damage. Toxicokinetic data showed delayed Tmax and plasma accumulation after 28 days of repeated ME exposure at doses of 20 mg/kg, 40 mg/kg, and 60 mg/kg. The metabolomic analysis pinpointed four critical pathways—TCA cycle; alanine, aspartate, and glutamate metabolism; arginine biosynthesis; and tyrosine metabolism—linked to 20 potential biomarkers. Gut microbiota analysis revealed that extended ME exposure led to microbial imbalance, particularly altering the populations of Akkermansia, Prevotella, and Ruminococcus, which are key to amino acid metabolism and the TCA cycle, thus contributing to hepatotoxicity. However, the causal relationship between changes in gut microbiota and liver metabolite levels still requires further in-depth research. This study underscores the significant role of liver metabolites and gut microbiota in ME-induced liver damage.

Two new species of Agaricales, Deconica flavum and Entocybe roseoalbus, are described from Mount Tianmu, Zhejiang Province, Eastern China. Two new species are distinct and monophyletic based on morphology and phylogenetic analyses. Deconica flavum differs from other Deconica species in that the pileus is brow shallow in the center and stipe with yellowish white fibrils, scatted on litter under coniferous and broad-leaved mixed forest at 1162 m. Entocybe roseoalbus is distinguished from other species of Entocybe by nearly blue pileus and pinkish-white stipe, scatted on humus in similar forest conditions at 1025 m. The differences are discussed between the two new taxa and their similar species morphologically, and related species phylogenetically.

Abstract Background Chronic osteomyelitis is a highly prevalent and severe orthopaedic complication, representing a critical unresolved issue. The clinical symptoms of osteomyelitis are influenced by various factors, including geography, lifestyle, and pre-existing medical conditions.This study aims to provide theoretical basis for treatment and prevention of osteomyelitis by investigating and analyzing clinical features and pathogen distribution among 282 patients with chronic tibial osteomyelitis in xinjiang. Methods A total of 282 patients with chronic tibial osteomyelitis from January 1, 2012 to January 1, 2022 in the First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed. All data were collected from electronic medical record (EMR) system including demographics, etiology, risk factors, osteomyelitis location and clinical classification. Results Farmers, students, unemployed and retirees accounted for a relatively large proportion of the 282 patients. There were 233 males and 49 females with a gender ratio of 4.75:1. The average age was 40.21 ± 15.68 years and was mainly concentrated in 41–50 years, specifically, the mean age of females was slightly older than that of males. Education level was mostly primary and secondary school education, and illiteracy. Risk factors of chronic tibial osteomyelitis included history of smoking and drinking, history of multiple repeated surgeries, and impaired immunity. Frequent clinical symptoms were in the order of pain, local swelling, pus discharge and skin ulceration. Among all inflammatory markers, proportion of positive results were 30.85%, 59.93% and 53.90% for white blood cell (WBC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), respectively. Positive rate of pathogenic microorganism culture was low and the three most common bacteria were Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli). The most frequent site of infection was middle tibia. According to Cierny-Mader osteomyelitis classification, the most common types were type IIIA, IVA and IIA. Conclusion Number of visits due to chronic osteomyelitis increased year by year, with young and middle-aged male farmers and low education level as the main groups. Smoking and drinking were two considerable risk factors that should be attached to a great importance. No significant increase was found in inflammatory markers and lower positive rate of pathogenic microorganism culture was observed. Multi-drug resistant bacteria were common and S. aureus remained the most frequent pathogen. Elevated ESR had certain diagnostic value for osteomyelitis. Type III and type IV osteomyelitis accounted for a large proportion which posed great challenges for clinical diagnosis and treatment.

Abstract Background Hyperglycemia is one of the most common comorbidities in patients with acute ischemic stroke (AIS). This study aimed to assess the impact of short-term longitudinal blood glucose level change trajectories on the 30-day mortality risk in patients with AIS. Methods Data for AIS patients were obtained from the 2001–2019 Medical Information Mart for Intensive Care (MIMIC) database. The latent growth mixture modeling (LGMM) was utilized to classify a patient’s blood glucose level trajectory within 24 h of admission. Cox regression analyses were applied to examine the relationship between blood glucose levels at admission and blood glucose level trajectories and the risk of 30-day mortality in patients with AIS. Results A total of 2,432 patients with AIS were included in this retrospective cohort study, with 30-day mortality occurring in 574 (23.60%) patients. The median glucose levels of all patients were 136.00 (110.00, 178.00) mg/dL. Four blood glucose level trajectories were identified: low level-stable trend (type 1), moderate level-stable trend (type 2), high level-decreasing-increasing trend (type 3), and moderate level-increasing-decreasing trend (type 4). Type 2 blood glucose level trajectory was associated with an increased risk of 30-day mortality compared with type 1 blood glucose level trajectory [hazard ratio (HR) = 1.28, 95% confidence interval (CI): 1.03–1.59), but there were no significant associations between type 3 (HR = 1.16, 95%CI: 0.77–1.74) and type 4 (HR = 1.44, 95%CI: 0.84–2.45) trajectories and 30-day mortality risk. Subgroup analysis demonstrated that the association between type 2 trajectory and 30-day mortality risk was observed in patients aged ≥ 65 years (HR = 1.37, 95%CI: 1.05–1.79), female (HR = 1.42, 95%CI: 1.05–1.94), with (HR = 1.44, 95%CI: 1.02–2.02) or without (HR = 1.42, 95%CI: 1.01–1.99) diabetes, and not using insulin (HR = 2.80, 95%CI: 1.43–5.49). Conclusion AIS patients with consistently high blood glucose levels within 24 h of admission increased the risk of 30-day mortality.

Abstract To efficiently realize the parallel task scheduling of SaaS platform in large-scale cloud service environment, this paper studies the parallel task scheduling algorithm of SaaS platform based on dynamic adaptive particle swarm optimization in cloud service environment. Users access the cloud through the user access interface module, and issue task scheduling instructions or send task scheduling requests. After the service management module provides diversified application service support according to the scheduling requirements, the core service module determines the SaaS platform parallel scheduling objective function, and uses dynamic adaptive particle swarm optimization to solve the objective function to obtain the SaaS platform parallel task scheduling results. The test results show that the algorithm has better multi-objective solving ability and can obtain higher quality objective solutions, and the test results of the total execution time of parallel scheduling tasks and the total transmission time of task data on SaaS platform are all within 30 s. The results of virtual machine resource load balancing degree are all below 15%; the utilization rate of virtual machine resources is above 92.2%.

A series of star-shaped multi-arm styrene-butadiene copolymers (S-g-SSB-6) were synthesized by living anionic polymerization, with n-butyllithium as initiator, styrene and butadiene as monomers, 2,2-di(tetra-hydrofuran-2-yl) propane as polar structure regulator and hexachlorodisilane as coupling agent. The molecular weight and its distribution, coupling arm number and coupling efficiency of S-g-SSB-6 were characterized by gel permeation chromatogram. The rheological properties of S-g-SSB-6, star-shaped multi-arm styrene-butadiene copolymer with SiCl4 as coupling agent, and linear styrene-butadiene copolymer (L-SSB) were characterized by rotational rheometer, and the effects of branched chain length and branched chain flexibility on the rheological properties of S-g-SSB-6 were also investigated. The results showed that the coupling arm numbers of S-g-SSB-6 reached 4.1, and the coupling efficiency was greater than 80%. S-g-SSB had lower melt viscosity and better fluid flow than those of L-SSB under the same weight-average molecular weight. When the branching degree was the same, the melt viscosity of S-g-SSB-6 increased with the increase of single arm molecular weight and molecular chain rigidity.

Abstract Background Coronaviruses (CoVs) represent a serious threat to human health and have become a major transmissible, endemic, and causative pathogen in humans; they represent a major health concern, given their ability to cause infectious diseases. Bats are natural hosts for diverse viruses. Many transmission events of CoVs and identification of multiple novel CoVs in bats has increased attention towards their capacity to serve as hosts for zoonotic viruses. Results In this study, 61 bats from Yunnan Province were analyzed, identifying seven CoVs, including three α- and two β-CoVs with full-genome sequences. Among the five identified alpha-CoVs, four belong to the Decacovirus subgenus and one to the Minunacovirus subgenus. Two beta-CoVs were also identified, both belonging to the Sarbecovirus subgenus.The genetic structures revealed similarities to known strains such as HKU10 and SARS-CoV-2, along with novel findings such as the Minunacovirus subgenus CoV YJ3c/f and unique ORF patterns. Our results demonstrated that strain JCC9 has a unique recombination pattern and shows a higher binding affinity to civet and pangolin ACE2 receptors, then the HpJC8xc strain transmits and recombines between hosts (bats), indicating a potential risk of crossing the interspecies barrier and infecting other animals. Conclusions The CoVs detected in the bats studied in this research exhibit high diversity. Genomic analysis revealed that CoVs in bats undergo frequent recombination events. Furthermore, recombination patterns and evolutionary analyses suggest that alpha-CoVs are more prone to cross-species transmission across different bat families/genera, whereas beta-CoVs demonstrate host specificity and tend to co-evolve with their bat hosts.Our finding suggest that bats, as hosts of CoVs, be constantly monitored to prevent outbreaks of new infections caused by viruses passing across interspecies barriers, and consequently, viral diseases in humans or livestock.

Abstract IL-1β represents an important inflammatory factor involved in the host response against GBS infection. Prior research has suggested a potential involvement of IL-1β in the process of ferroptosis. However, the relationship between IL-1β and ferroptosis in the context of anti-GBS infection remains uncertain. This research demonstrates that the occurrence of ferroptosis is essential for the host’s defense against GBS infection in a mouse model of abdominal infection, with peritoneal macrophages identified as the primary cells undergoing ferroptosis. Further research indicates that IL-1β induces lipid oxidation in macrophages through the upregulation of pathways related to lipid oxidation. Concurrently, IL-1β is not only involved in the initiation of ferroptosis in macrophages, but its production is intricately linked to the onset of ferroptosis. Ultimately, we posit that ferroptosis acts as a crucial initiating factor in the host response to GBS infection, with IL-1β playing a significant role in the resistance to infection by serving as a key inducer of ferroptosis.

In this study, on the basis of single factor experiments, the effects of raw material mass concentration, ethanol volume fraction, ultrasonic power, extraction temperature, and extraction time on the lipase inhibition activity of mulberry leaves extract were investigated in combination with response surface methodology to optimize the ultrasonic-assisted extraction process of the lipase-inhibiting components of mulberry leaves. Meanwhile, the active ingredients of mulberry leaves extract were analyzed by UPLC-Q-TOF HRMS. The results showed that the optimal extraction process parameters for the lipase-inhibiting components of mulberry leaves were as follows: The mass concentration of raw material was 0.05 g/mL, volume fraction of ethanol was 70%, ultrasonic power was 195 W, extraction temperature was 31 ℃ and the extraction time was 40 min. Under these conditions, the lipase inhibition rate of mulberry leaves extract was 39.68%. A total of 1067 compounds were identified. Flavonoids and phenolic acids accounted for the highest proportion, containing 203 and 201 compounds, respectively. These compounds might be the material basis for the lipase inhibiting activity of mulberry leaves extract. In this study, the ultrasonic-assisted extraction process of mulberry leaves was optimized to improve the extraction efficiency of the lipase-inhibiting active components, and the main active ingredients were analyzed. The results may provide a reference for the functional application of mulberry leaves in improving lipid metabolism and the development of health food.

Abstract The use of natural gas pipeline networks to transmit hydrogen energy is an important form of hydrogen energy utilisation. The coupling of hydrogen‐enriched natural gas pipeline network and power grid involves the energy conversion of electricity‐hydrogen‐electricity, so the assessment is crucial because the system is complex, and the hazards to the system can be identified. This paper proposes a risk assessment method for gas‐electric coupling of hydrogen‐enriched natural gas pipeline networks and a three‐stage risk assessment model to assess the life cycle risk of natural gas pipelines; a material energy‐based risk transfer model considering gas‐electric coupling is proposed to describe the risk transfer process of hydrogen‐enriched natural gas between the gas network and the grid. By comparing and analysing the risk of natural gas blending ratio to the pipeline and the risk of pipeline pressure to the pipeline, the validity of the model is verified, which provides safety support for the connection of the natural gas pipeline system to the grid and ensures the efficient use of hydrogen energy.

Abstract Background Lipid levels have been suggset to be correlated with multiple myeloma (MM) risk, though causality remains unconfirmed. To explore this further, a detailed study combining meta-analysis and Mendelian randomization (MR) was conducted. Methods Literature searches were performed on PubMed and Embase; summary data for plasma lipid traits were extracted from the IEU and MM data from the FinnGen database. Meta-analysis and MR were utilized to analyze the link of lipids with MM risk, including mediator MR to identify potential mediators. The study was conducted in accordance with PRISMA and STROBE-MR guidelines. Results Observational studies analyzed through meta-analysis showed that elevated levels of LDL, HDL, total cholesterol (TC), and triglycerides correlate with a lower risk of MM, with HRs of 0.73, 0.59, 0.60, and 0.84, respectively. MR analysis confirmed a potential causal link of triglyceride with a reduced MM risk (OR: 0.67, 95% CI: 0.46–0.98), independent of BMI. Mediation analysis pointed to X-11,423-O-sulfo-L-tyrosine and neuropilin-2 as potential mediators. Conclusions The findings suggest that higher lipid levels (LDL, HDL, TC, and triglycerides) are linked with a reduced MM risk, and higher triglyceride levels are causally associated with a reduced MM risk. This suggests new avenues for therapeutic interventions targeting MM.

Abstract As one of the most prevalent tumors, colorectal cancer (CRC) owns complex pathogenesis and the high recurrence rate significantly influence the prognosis of patients with KRAS mutant CRC, to discovery the crosstalk among KEAP1‐NFE2L2 and oncogenic KRAS as the potential prognostic biomarkers in CRC, which might be used to develop novel and effective therapeutics. By using bioinformatics analysis, we explored and identified key genes as the predicted targets in the crosstalk among KEAP1 oncogenic signatures of KRAS mutation that were linked with development, metastasis, and poor prognosis in CRC. We further investigated the correlations between the clinical characteristics and expressions of prognostic genes among the KRAS and KEAP1‐related key hub genes in CRC, which as predicted targets to find the potential herbal ingredients in HERB database, further to verify the active herbal ingredients could regulate the key targets that related to KEAP1‐NFE2L2 in KRAS mutant CRC. The newest TCGA data reveals that the mutation of KRAS is found in 44% of CRC patients. In total, 28 genes were identified as differentially expressed genes (DEGs), and the hub genes such as CDKN2A, SPP1, FOS, BCL2L11, and HPSE were verified. Results indicated that key genes (SOX9, SPP1) significant correlation with the target prediction of the active herbal ingredients by molecular docking analysis. Furthermore, KEAP1, NFE2L2, SOX9 expression were decreased significantly with the treatment of potential ingredients. Furthermore, cyclopamine could enhance the sensitivity of HCT116 cells, downregulated the expression of SPP1, and induced activation of KEAP1‐NFE2L2 pathway, which cell death are characteristic features of apoptosis, and enhanced anticancer effect. Therefore, KEAP1‐related genes might be important oncogenic signatures in KRAS mutant CRC cells and cyclopamine was identified as a potential ingredient and regulated the predict targets of SOX9 and SPP1, may be expand the efficacy and range of novel and effective therapeutics.

This study examines the microstructural evolution, elemental distribution, phase composition, and hardness variations in multi-material samples fabricated using Laser Powder Bed Fusion (LPBF) with Invar and Ti6Al4V with compositional gradients mediated by copper. A range of compositional transitions from Invar to Ti6Al4V with different copper fractions are reported. Defects such as gas and keyhole pores were detected in well-deep keyhole mode areas, while lack of fusion defects were observed in samples with pure Cu interlayers due to poor wettability and processing parameter variations. Crack formation between interlayer gradient zones and Invar regions was linked to FeNi and CuNi intermetallic phases. Intermetallic compounds (e.g., FeNi, CuNi, TiFe, TiNi) significantly influenced the microstructure and mechanical performance. Vickers hardness testing shows varying hardness across different builds, with the highest hardness being observed in the gradient zone enabled by pure copper (approximately 620 HV). This study also underscores the need for tailored component design linking build processing parameters and compositional transitions in multi-material LPBF to achieve desired properties and component structural behaviour.

Abstract Background There is a paucity of data regarding sex-oriented analyses of connection between muscle quantity and quality and health-related quality of life (HRQoL), taking into account the pathophysiological differences of sarcopenia/myosteatosis in males versus females. We sought to investigate the associations between skeletal muscle index (SMI)-defined sarcopenia and intramuscular adipose tissue content (IMAC)-defined myosteatosis and EuroQol-5D (EQ-5D)-defined HRQoL in patients with decompensated cirrhosis concerning sex disparities. Methods Totally, 382 patients were enrolled. The relationship between SMI/IMAC and HRQoL was evaluated with restricted cubic spline and Pearson correlation analyses. Furthermore, association between SMI or sarcopenia and EQ-5D utility index was determined by multiple linear regression, adjusted for age, BMI and concurrent disease severity. Results The study population comprised evenly distributed male and female patients (190: 192), mean age 61.9 years. The prevalence of sarcopenia (40.5 versus 9.9%, P

Abstract Objective To evaluate the clinical outcomes of arthroscopic inside-out ganglionectomy of dominant dorsal wrist ganglion. Methods Patients with dominant wrist ganglion cyst treated in our hospital from January 1, 2014 to June 31, 2023 was enrolled in this retrospective analysis. All patients underwent dye-assist arthroscopic inside-out ganglionectomy. After discharge, the patients were followed for a minimum of 6 months. The primary outcomes were to assess patient wrist function using the Patient-Rated Wrist Evaluation (PRWE) and Mayo Modified Wrist Score (MMWS). The secondary outcomes were visual analog score (VAS), wrist active range of motion (ROM), grip strength, recurrence rate and complication. Results All ganglion were successfully resected after dye staining. Patients were followed for an average of 12.17 months. There were no significant changes between preoperative and postoperative wrist active ROM or grip strength, except for wrist flexion (which showed a slightly greater improvement after surgery, P = 0.049), there were notable improvements in VAS, MMWS, and PRWE postoperatively. Recurrence occurred in 3 patients. No major complications observed during the follow-up period. Conclusion Dye-assist arthroscopic inside-out ganglionectomy is safe and uncomplicated, worth of clinical promotion.

Abstract Background To mitigate hospital-acquired transmission of coronavirus disease 2019 (COVID-19), various prevention and control measures have been strictly implemented in medical institutions. These stringent measures can potentially reduce the incidence of hospital-acquired respiratory infections. This study aimed to assess if there were changes in the prevalence of hospital-acquired respiratory infections during a period of national attention focused on COVID-19 prevention. Methods A retrospective analysis of the clinical data from adult patients with hospital-acquired respiratory infections admitted between October and December 2019 and during the same period in 2020 was performed. All patients were referred from a general hospital in Beijing China and COVID-19 patients were not treated at the hospital. Hospital-acquired respiratory infections were diagnosed based on the criteria of the Centers for Disease Control and Prevention/National Healthcare Safety Network (CDC/NHSN). A comparison of the incidence and mortality rate of hospital-acquired respiratory infections between the two selected time periods was conducted. Additionally, multivariate logistics regression analysis was used to identify mortality-associated risk factors. Results This study included 2,211 patients from October to December 2019 (pre-COVID-19 pandemic) and 2,921 patients from October to December 2020 (during the COVID-19 pandemic). The incidence of hospital-acquired respiratory infections in 2019 and 2020 was 4.7% and 2.9%, respectively, with odds ratio (OR): 0.61, 95% confidence interval (CI): 0.46–0.81, and P = 0.001. In-hospital mortality of hospital-acquired respiratory infections in 2019 and 2020 was 30.5% and 38.4%, respectively, with OR: 1.42, 95%CI: 0.78–2.59, and P = 0.25. Multivariate logistics regression analysis revealed that a history of previous malignancy (OR: 2.50, 95%CI: 1.16–5.35, P = 0.02), was associated with in-hospital mortality. Conclusions The incidence of hospital-acquired respiratory infections was significantly decreased following the implementation of various prevention and control measures during the COVID-19 pandemic. A history of previous malignancy was associated with higher in-hospital mortality in older inpatients with hospital-acquired respiratory infections.

Abstract Background After a 920-day hiatus, COVID-19 resurged in the Tibet Autonomous Region of China in August 2022. This study compares the characteristics of COVID-19 between high-altitude residents and newcomers, as well as between newcomers and lowlanders. Methods This multi-center cohort study conducted at the Third People’s Hospital of Tibet Autonomous Region and Beijing University Shenzhen Hospital, included 520 high-altitude resident patients, 53 high-altitude newcomer patients, and 265 lowlander patients infected with the Omicron variant. Initially, we documented epidemiological, clinical, and treatment data across varying residency at admission. We compared the severity of COVID-19 and various laboratory indicators, including hemoglobin concentration and SpO2%, over a 14-day period from the date of the first positive nucleic acid test, as well as the differences in treatment methods and disease outcomes between highlanders and high-altitude newcomers. We also compared several characteristics of COVID-19 between high-altitude newcomers and lowlanders. Univariate analysis, multivariable logistic regression, and the generalized linear mixed model were utilized for the analysis. Results No fatalities were observed. The study found no significant differences in COVID-19 severity or in the physiological measures of hemoglobin concentration and SpO2% between high-altitude and lowland residents. Similarly, there were no statistically significant differences in the values or trends of hemoglobin and SpO2% between high-altitude residents and newcomers throughout the 14-day observation period. However, compared to age- and sex-matched lowlander patients (1:5 ratio), high-altitude newcomers exhibited higher heart rates, respiratory rates, and average hemoglobin concentrations, along with lower platelet counts. There were no significant differences in hospital stays between the two groups. Conclusions High-altitude residents and newcomer patients exhibit clinical similarities. However, the clinical characteristics of high-altitude newcomers and lowlander patients differ due to the impact of the high-altitude environment. These results highlight potential considerations for public health strategies in high-altitude regions such as Tibet.

Abstract In metazoans mitochondrial DNA (mtDNA) or retrotransposon cDNA released to cytoplasm are degraded by nucleases to prevent sterile inflammation. It remains unknown whether degradation of these DNA also prevents nuclear genome instability. We used an amplicon sequencing-based method in yeast enabling analysis of millions of DSB repair products. In non-dividing stationary phase cells, Pol4-mediated non-homologous end-joining increases, resulting in frequent insertions of 1–3 nucleotides, and insertions of mtDNA (NUMTs) or retrotransposon cDNA. Yeast EndoG (Nuc1) nuclease limits insertion of cDNA and transfer of very long mtDNA ( >10 kb) to the nucleus, where it forms unstable circles, while promoting the formation of short NUMTs (~45–200 bp). Nuc1 also regulates transfer of extranuclear DNA to nucleus in aging or meiosis. We propose that Nuc1 preserves genome stability by degrading retrotransposon cDNA and long mtDNA, while short NUMTs originate from incompletely degraded mtDNA. This work suggests that nucleases eliminating extranuclear DNA preserve genome stability.

Abstract Thermoelectrics converting heat and electricity directly attract broad attentions. To enhance the thermoelectric figure of merit, zT, one of the key points is to decouple the carrier-phonon transport. Here, we propose an entropy engineering strategy to realize the carrier-phonon decoupling in the typical SrTiO3-based perovskite thermoelectrics. By high-entropy design, the lattice thermal conductivity could be reduced nearly to the amorphous limit, 1.25 W m−1 K−1. Simultaneously, entropy engineering can tune the Ti displacement, improving the weighted mobility to 65 cm2 V−1 s−1. Such carrier-phonon decoupling behaviors enable the greatly enhanced μ W/κ L of ~5.2 × 103 cm3 K J−1 V−1. The measured maximum zT of 0.24 at 488 K and the estimated zT of ~0.8 at 1173 K in (Sr0.2Ba0.2Ca0.2Pb0.2La0.2)TiO3 film are among the best of n-type thermoelectric oxides. These results reveal that the entropy engineering may be a promising strategy to decouple the carrier-phonon transport and achieve higher zT in thermoelectrics.